Intergenerational Transmission of Psychiatric Conditions and Psychiatric, Behavioral, and Psychosocial Outcomes in Offspring.

Importance: Psychiatric conditions in parents are associated with many psychiatric and nonpsychiatric outcomes in offspring. However, it remains unknown whether this intergenerational transmission is attributable to broader psychopathology comorbidity or to specific conditions. Objective: To estimate associations between general and specific psychopathology factors in parents and a wide range of register-based outcomes in their offspring. Design, Setting, and Participants: This Swedish national register-based cohort study included 2 947 703 individuals born between 1970 and 2000 and followed up with participants through December 31, 2013. Statistical analysis was performed from October 2022 to October 2023. Exposures: Hierarchical factor model consisting of 1 general and 3 specific psychopathology factors fit to 9 parental psychiatric diagnoses and violent criminal court convictions. Main Outcomes and Measures: A total of 31 outcomes were measured in offspring and sorted into 6 broad clusters: psychotic-like outcomes, neurodevelopmental outcomes, internalizing outcomes, externalizing outcomes, behavior and accidents, and psychosocial outcomes. Results: Of 2 947 703 individuals, 1 518 252 (51.5%) were male, and the mean (SD) age at the end of follow-up was 28.7 (8.9) years. The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (range: odds ratio [OR] for accidents, 1.08 [95% CI, 1.07-1.08] to OR for social welfare recipiency, 1.40 [95% CI, 1.39-1.40]), which means that children whose parents scored 1 SD above the mean on the general psychopathology factor had an 8% to 40% higher odds of different studied outcomes. The specific psychotic factor in parents was primarily associated with all 5 psychotic-like outcomes (range: OR for prescription of antiepileptics, 1.05 [95% CI, 1.04-1.06] to OR for schizophrenia, 1.25 [95% CI, 1.23-1.28]) and the specific internalizing factor in parents was primarily associated with all 6 internalizing outcomes (range: OR for prescription of anxiolytics, 1.10 [95% CI, 1.09-1.10] to OR for depression, 1.13 [95% CI, 1.12-1.13]) and all 6 neurodevelopmental outcomes (range: OR for intellectual disability, 1.02 [95% CI, 1.01-1.03] to OR for autism spectrum disorder, 1.10 [95% CI, 1.09-1.11]) in offspring. The specific externalizing factor in parents was associated with all 6 externalizing outcomes (range: OR for violent crimes, 1.21 [95% CI, 1.19-1.23] to OR for oppositional defiant disorder, 1.32 [95% CI, 1.32-1.33]) and all 6 internalizing outcomes (range: OR for obsessive-compulsive disorder, 1.01 [95% CI, 1.00-1.02] to OR for posttraumatic stress disorder, 1.13 [95% CI, 1.12-1.13]) in offspring. Conclusions and Relevance: This cohort study of the Swedish population suggests that the intergenerational transmission of psychiatric conditions across different types of spectra may largely be attributable to a parental general psychopathology factor, whereas specific factors appeared to be primarily responsible for within-spectrum associations between parents and their offspring. Professionals who work with children (eg, child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental psychiatric conditions into account, regardless of type, when forecasting child mental health and social functions.

Prediction of reoffending risk in men convicted of sexual offences: development and validation of novel and scalable risk assessment tools (OxRIS).

Background: Current risk assessment tools have a limited evidence base with few validations, poor reporting of outcomes, and rarely include modifiable factors. Methods: We examined a national cohort of men convicted of sexual crimes in Sweden. We developed prediction models for three outcomes: violent (including sexual), any, and sexual reoffending. We used Cox proportional hazard regression to develop multivariable prediction models and validated these in an external sample. We reported discrimination and calibration statistics at prespecified cut-offs. Findings: We identified 16,231 men convicted of sexual offences, of whom 14.8% violently reoffended during a mean follow up of 38 months, 31.4% for any crime (34 months), and 3.6% for sexual crimes (42 months). Models for violent and any reoffending showed good discrimination and calibration. At 1, 3, and 5 years, the area under the curve (AUC) was 0.75-0.76 for violent reoffending and 0.74-0.75 for any reoffending. The prediction model for sexual reoffending showed modest discrimination (AUC = 0.67) and good calibration. We have generated three simple and web-based risk calculators, which are freely available. Interpretation: Scalable evidence-based risk assessment tools for sexual offenders in the criminal justice system and forensic mental health could assist decision-making and treatment allocation by identifying those at higher risk, and screening out low risk persons.

Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort.

Importance: Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings. Objective: To examine the association between CD and neurodevelopmental and psychiatric disorders in children. Design, Setting, and Participants: This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021. Exposures: Birth by CD recorded at birth, stratified into planned and intrapartum CD. Main Outcomes and Measures: Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder. Results: Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21). Conclusions and Relevance: The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.

Healthcare utilization and costs of psychiatric and somatic comorbidities associated with newly diagnosed adult ADHD.

BACKGROUND: Psychiatric and somatic problems in young adulthood have been found to be main drivers of costs in individuals with childhood ADHD. However, knowledge of the patterns of healthcare utilization and costs of comorbidities in middle-aged adults with newly diagnosed ADHD is very limited. METHOD: We studied individuals born 1966-1978 (from the Swedish Total Population Register) with newly diagnosed ADHD between the ages of 30-45 years and individuals without ADHD matched on birthdate, birth county, and sex. Healthcare utilization and expenditure for psychiatric and somatic disorders were obtained over four years (two years pre- and post-initial ADHD diagnosis). RESULTS: Middle-aged adults with newly diagnosed ADHD showed higher levels of healthcare utilization and costs (outpatient, inpatient, medications) for psychiatric and somatic comorbidities relative to adults without ADHD, both before and after the initial diagnosis. Females showed greater average group differences across the study period for medication prescriptions than males. Total incremental annual costs per capita were €2478.76 in adults with ADHD relative to those without, and costs were mainly driven by inpatient care. Psychiatric outpatient visits were statistically significantly higher the year before the ADHD diagnosis compared with two years before and after the diagnosis. CONCLUSION: This study demonstrates the substantial burden of psychiatric and somatic comorbidities in middle-aged adults newly diagnosed with ADHD. Psychiatric outpatient visits peaked in the year leading up to the ADHD diagnosis. Findings further suggested that females with ADHD may seek more treatment for comorbidities than males, which may reflect a general female tendency.

Assessment of Posttraumatic Stress Disorder and Educational Achievement in Sweden.

Importance: Posttraumatic stress disorder (PTSD) has been associated with impaired educational performance. Previous studies on the disorder could not control for important measured and unmeasured confounders. Objective: To prospectively investigate the association between PTSD and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability. Design, Setting, and Participants: This population-based cohort study included 2 244 193 individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed-up until December 31, 2013. Clusters of full siblings were used to account for familial factors. Data analyses were conducted between December 2018 and May 2020. Exposure: International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of PTSD in the Swedish National Patient Register. Main Outcomes and Measures: Eligibility to access upper secondary education after finishing compulsory education, finishing upper secondary education, starting a university degree, and finishing a university degree. Results: Of the final cohort of 2 244 193 individuals (1 151 414 [51.3%] men) included in the analysis, 1 425 326 were assessed for finishing compulsory education (919 with PTSD), 2 001 944 for finishing upper secondary education (2013 with PTSD), and 1 796 407 and 1 356 741 for starting and finishing a university degree (2243 and 2254 with PTSD, respectively). Posttraumatic stress disorder was associated with lower odds of achieving each of the educational milestones during the study period, including 82% lower odds of finishing compulsory education (adjusted odds ratio [aOR], 0.18; 95% CI, 0.15-0.20), 87% lower odds of finishing upper secondary education (aOR, 0.13; 95% CI, 0.12-0.14), 68% lower odds of starting a university degree (aOR, 0.32; 95% CI, 0.28-0.35), and 73% lower odds of finishing a university degree (aOR, 0.27; 95% CI, 0.23-0.31). Estimates in the sibling comparison were attenuated (aOR range, 0.22-0.53) but remained statistically significant. Overall, excluding psychiatric comorbidities and adjusting for the successful completion of the previous milestone and general cognitive ability did not statistically significantly alter the magnitude of the associations. Conclusions and Relevance: Posttraumatic stress disorder was associated with educational impairment across the life span, and the associations were not entirely explained by shared familial factors, psychiatric comorbidity, or general cognitive ability. This finding highlights the importance of implementing early trauma-informed interventions in schools and universities to minimize the long-term socioeconomic consequences of academic failure in individuals with PTSD.

Clinical Characteristics and Pharmacological Treatment of Individuals With and Without Intellectual Disability in Pre-trial Assessment-A Population-Based Study.

Background: The current lack of knowledge about intellectual disability (ID) in forensic psychiatric contexts can compromise the legal certainty of these individuals during the medico-legal process. To address ambiguous results in previous literature, the aim of the current study was to estimate the prevalence of ID in a pre-trial forensic psychiatric settings. Moreover, as little is known about the characteristics of offenders with ID, we conducted a clinical characterization of individuals with and without ID being subject to forensic psychiatric assessment. Methods: Using data from several Swedish national registers, we conducted a population-based retrospective observational study on 8,442 individuals being subject to pre-trial forensic psychiatric assessments in Sweden in 1997-2013. We performed univariate analyses to compare the characteristics of individuals with (n = 537) and without ID (n = 7,905). Results: The prevalence of ID was 6.4% in the Swedish pre-trial forensic psychiatric context during the observational period. Compared with individuals without ID, individuals with ID were younger at the time of assessment, had a lower educational level, and had less frequently started families. ID was associated with lower frequency of diagnosed psychotic and bipolar disorders. However, a similar prescription rate of antipsychotics, and a comparable rate of previous inpatient care was observed among individuals with and without ID. Individuals with ID had more often been prescribed anti-libidinal treatments often used for treating sexual disorders, although did not present a higher prevalence of sexual disorder. Conclusions: The prevalence of ID among pre-trial individuals being subject to forensic psychiatric assessment was more than twice as high as assumed in the general population. Our results suggest that individuals with ID received pharmacotherapy without clear indication. Remaining challenges in the clinical management of individuals with ID were indicated by the discrepancy between the occurrence of psychiatric diagnoses, pharmacological treatment patterns, and rates of inpatient care.

Trajectories of healthcare utilization and costs of psychiatric and somatic multimorbidity in adults with childhood ADHD: a prospective register-based study.

BACKGROUND: A better understanding of the trajectories and economic burden of psychiatric and somatic disorders (multimorbidity) in ADHD from childhood to adulthood is important for guiding more targeted areas for treatment of ADHD and prevention of multimorbidity, and for forecasting demands on the medical infrastructure. This study aimed to investigate patterns of healthcare utilization and costs of multimorbidity across young adulthood in individuals with a childhood ADHD diagnosis, and additionally in individuals who continue to have ADHD-related contact with health services (persisters) and those who do not (remitters). METHODS: We prospectively followed a cohort (N = 445,790) born 1987-1990 from the ages of 18 to 26 years. Data on healthcare utilization were obtained from the Swedish National Patient Register (inpatient and outpatient care) and the Prescribed Drug Register (medication prescriptions). RESULTS: Mean annual costs per capita from multimorbidity was €890 ($1,223) in individuals with a childhood ADHD diagnosis (persisters/remitters: €1,060[$1,456]/€609[$837]) and €304 ($418) in individuals without. Costs were largely driven by inpatient hospital admissions, mainly from drug abuse and injuries. Healthcare utilization and costs of psychiatric and somatic disorders at 18 years was significantly higher in individuals with childhood ADHD compared to those without. These group differences remained stable or increased across young adulthood for most outcomes and were generally larger in women than in men. ADHD remitters continued to show significantly greater healthcare utilization and costs compared to individuals without childhood ADHD, although their profiles were not as severe as ADHD persisters. CONCLUSIONS: Childhood ADHD has long-term associations with both psychiatric and somatic disorders. Findings demonstrate the individual and societal burden of ADHD in adulthood and highlight the importance of continued support from childhood-adolescent to adult health services and early prevention of multimorbidity. Findings also point to specific targets for intervention that may be effective, such as drug abuse and injuries.

Associations between conduct problems in childhood and adverse outcomes in emerging adulthood: a longitudinal Swedish nationwide twin cohort.

BACKGROUND: We examined whether childhood conduct problems predicted a wide range of adverse outcomes in emerging adulthood and whether the association with internalizing problems remained after adjusting for general comorbidity and externalizing problems. METHODS: Participants were 18,649 twins from the Child and Adolescent Twin Study in Sweden. At age 9/12, parents rated their children on eight conduct problems. Adverse outcomes were retrieved from national registers in emerging adulthood (median follow-up time = 9.2 years), including diagnoses of six psychiatric disorders, prescriptions of antidepressants, suicide attempts, criminality, high school ineligibility, and social welfare recipiency. We estimated risk for the separate outcomes and examined if conduct problems predicted an internalizing factor above and beyond a general comorbidity and an externalizing factor. We used twin analyses to estimate genetic and environmental contributions to these associations. RESULTS: On the average, each additional conduct symptom in childhood was associated with a 32% increased risk of the adverse outcomes in emerging adulthood (mean hazard ratio = 1.32; range = 1.16, 1.56). A latent childhood conduct problems factor predicted the internalizing factor in emerging adulthood (ßboys  = .24, standard error, SE = 0.03; ßgirls  = .17, SE = 0.03), above and beyond its association with the externalizing (ßboys  = 0.21, SE = 0.04; ßgirls  = 0.17, SE = 0.05) and general factors (ßboys  = 0.45, SE = 0.03; ßgirls  = 0.34, SE = 0.04). These associations were differentially influenced by genetic and environmental factors. CONCLUSIONS: It is important to monitor boys and girls with conduct problems not only for future externalizing problems, but also for future internalizing problems. Prevention of specific outcomes, however, might require interventions at different levels.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

BACKGROUND: Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS: To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS: Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.

A register-based case-control study of health care utilization and costs in binge-eating disorder.

OBJECTIVE: Capturing trends in healthcare utilization may help to improve efficiencies in the detection and diagnosis of illness, to plan service delivery, and to forecast future health expenditures. For binge-eating disorder (BED), issues include lengthy delays in detection and diagnosis, missed opportunities for recognition and treatment, and morbidity. The study objective was to compare healthcare utilization and expenditure in people with and without BED. METHODS: A case-control design and nationwide registers were used. All individuals diagnosed with BED at eating disorder clinics in Sweden between 2005 and 2009 were included (N = 319, 97% female, M age = 22 years). Ten controls (N = 3190) were matched to each case on age-, sex-, and location of birth. Inpatient, hospital-based outpatient, and prescription medication utilization and expenditure were analyzed up to eight years before and four years after the index date (i.e., date of diagnosis of the BED case). RESULTS: Cases had significantly higher inpatient, hospital-based outpatient, and prescription medication utilization and expenditure compared with controls many years prior to and after diagnosis of BED. Utilization and expenditure for controls was relatively stable over time, but for cases followed an inverted U-shape and peaked at the index year. Care for somatic conditions normalized after the index year, but care for psychiatric conditions remained significantly higher. CONCLUSION: Individuals with BED had substantially higher healthcare utilization and costs in the years prior to and after diagnosis of BED. Since previous research shows a delay in diagnosis, findings indicate clear opportunities for earlier detection and clinical management. Training of providers in detection, diagnosis, and management may help curtail morbidity. A reduction in healthcare utilization was observed after BED diagnosis. This suggests that earlier diagnosis and treatment could improve long-term health outcomes and reduce the economic burden associated with BED.

Neighborhood Influences on Violent Reoffending Risk in Released Prisoners Diagnosed With Psychotic Disorders.

Released prisoners diagnosed with psychotic disorders have elevated rates of violent reoffending risk and their exposure to adverse neighborhood environments may contribute to this risk. We identified all released sentenced prisoners in Sweden between 2003 and 2013 (n = 47226) and followed them up for a median period of 4.4 years. We identified prisoners who had ever been diagnosed with a psychotic disorder (n = 3782) or prescribed antipsychotics (n = 7366). We examined 3 neighborhood characteristics: income, proportion of welfare recipients, and crime rate. By fitting generalized mixed-effects and negative binomial regression models and adopting within-individual designs that controlled for all time-invariant unmeasured confounders within each individual, we estimated neighborhood intraclass correlations (ICCs) and associations between specific neighborhood characteristics and violent reoffending. Neighborhood factors explained 13.5% (95% CI: 10.9%; 16.6%) of the violent reoffending risk among released prisoners diagnosed with psychotic disorders. This contrasted with 4.3% (95% CI: 3.7%; 4.9%) in all released prisoners. However, after controlling for unmeasured confounding, these estimates were not statistically significant (ICCpsychotic disorders = 0.9%; 95% CI: -0.8%; 2.3%; ICCall prisoners = 0.3%; 95% CI: -0.02%; 0.6%). Similarly, none of the within-individual correlations between the specific neighborhood factors and violent reoffending were significantly different from zero. We found consistent results when we investigated prisoners with other psychiatric and substance use disorders. These findings suggest that placing released prisoners with psychotic disorders in less deprived neighborhoods might not reduce their violent reoffending risk, which may also apply to other psychiatric disorders. The assessment, treatment, and community linkage of high-risk prisoners as a strategy to reduce reoffending needs further research.

Assessment of muscle function using hybrid PET/MRI: comparison of 18F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects.

PURPOSE: The aim of this study was to determine the relationship between relative glucose uptake and MRI T 2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. METHODS: Ten young healthy recreationally active men (age 21 - 28 years) were injected with 18F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18F-FDG PET/MRI and muscle groups were evaluated for increases in 18F-FDG uptake and MRI T 2 values. RESULTS: A significant linear correlation between 18F-FDG uptake and changes in muscle T 2 (R 2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18F-FDG uptake and changes in muscle T 2 did not vary among subjects. CONCLUSION: This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between 18F-FDG uptake and changes in muscle T 2 with physical exercise. Accordingly, it seems that changes in muscle T 2 may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies.

A Register-Based Case-Control Study of Prescription Medication Utilization in Binge-Eating Disorder.

OBJECTIVE: Individuals with binge-eating disorder (BED) experience psychiatric and somatic comorbidities and obesity, but the nature and magnitude of prescription medication utilization is unclear. We investigated utilization using Swedish registry data and a case-control design. METHODS: Cases were identified from Riksät and Stepwise longitudinal registers and were individuals diagnosed with BED per DSM-IV-TR criteria between July 1, 2006, and December 31, 2009, at eating disorder clinics (n = 238, 96% female, mean age = 22.8 years). For each case, 10 controls were matched on sex and year, month, and county of birth (n = 2,380). An index date was derived for each control, which was the date of diagnosis of BED in the corresponding case. The association between BED and prescription medication utilization was investigated before and within 12 months after diagnosis. RESULTS: Before diagnosis, cases were significantly more likely than matched controls to have been prescribed nervous system (odds ratio = 6.4; 95% confidence limit = 4.7, 8.6), tumors and immune disorders (3.5; 1.3, 9.3), cardiovascular (2.2; 1.4, 3.5), digestion and metabolism (2.1; 1.5, 2.9), infectious diseases (1.9; 1.4, 2.6), skin (1.8; 1.3, 2.5), and respiratory system (1.3; 1.0, 1.8) medications. Cases also had higher odds of prescription use than controls across most categories within 12 months after diagnosis. Several associations were significant after accounting for lifetime psychiatric comorbidity and obesity. CONCLUSIONS: Individuals with BED had increased utilization of psychiatric and nonpsychiatric medications compared with matched controls. Findings confirm that the illness burden of BED extends to high medication utilization and underscore the importance of thorough medication reviews when treating individuals with BED.

Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison.

BACKGROUND: It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. AIMS: To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. METHOD: We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. RESULTS: In the population, lower birth weight (⩽ 2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. CONCLUSIONS: Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems.

Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia.

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia.

Family income in early childhood and subsequent attention deficit/hyperactivity disorder: a quasi-experimental study.

BACKGROUND: Studies have found negative associations between socioeconomic position and attention deficit/hyperactivity disorder (ADHD), but it remains unclear if this association is causal. The aim of this study was to determine the extent to which the association between family income in early childhood and subsequent ADHD depends on measured and unmeasured selection factors. METHODS: A total of 811,803 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Diagnosis of ADHD was assessed via the Swedish national Patient Register and the Swedish Prescribed Drug Register. Annual family income during offspring's first 5 years in life was collected prospectively from the Swedish Integrated Database for Labour Market Research and divided into quartiles by (lower) family disposable income. We predicted ADHD from family income while controlling for covariates and also comparing differently exposed cousins and siblings to control for unmeasured familial confounding. RESULTS: The crude analyses suggested that children exposed to lower income levels were at increased risk for ADHD (HRQ uartile1  = 2.52; 95% CI, 2.42-2.63; HRQ uartile2  = 1.52; 95% CI, 1.45-1.58; HRQ uartile3  = 1.20; 95% CI, 1.14-1.15). This dose-dependent association decreased after adjustment for measured covariates (HRQ uartile1  = 2.09; 95% CI, 2.00-2.19; HRQ uartile2  = 1.36; 95% CI, 1.30-1.42; HRQ uartile3  = 1.13; 95% CI, 1.08-1.18). Although the association was attenuated in cousin comparisons (HRQ uartile1  = 1.61; 95% CI, 1.40-1.84; HRQ uartile2  = 1.28; 95% CI, 1.12-1.45; HRQ uartile3  = 1.14; 95% CI, 1.01-1.28) and sibling comparison models (HRQ uartile1  = 1.37; 95% CI, 1.07-1.75; HRQ uartile2  = 1.37; 95% CI, 1.12-1.68; HRQ uartile3  = 1.23; 95% CI, 1.04-1.45), it remained statistically significant across all levels of decreased disposable family income. CONCLUSIONS: Our results indicated that low family income in early childhood was associated with increased likelihood of ADHD. The link remained even after controlling for unmeasured selection factors, highlighting family income in early childhood as a marker of causal factors for ADHD.

Preterm birth and mortality and morbidity: a population-based quasi-experimental study.

IMPORTANCE: Preterm birth is associated with increased mortality and morbidity. However, previous studies have been unable to rigorously examine whether confounding factors cause these associations rather than the harmful effects of being born preterm. OBJECTIVE: To estimate the extent to which the associations between early gestational age and offspring mortality and morbidity are the result of confounding factors by using a quasi-experimental design, the sibling-comparison approach, and by controlling for statistical covariates that varied within families. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study, combining Swedish registries to identify all individuals born in Sweden from 1973 to 2008 (3,300,708 offspring of 1,736,735 mothers) and link them with multiple outcomes. MAIN OUTCOMES AND MEASURES: Offspring mortality (during infancy and throughout young adulthood) and psychiatric (psychotic or bipolar disorder, autism, attention-deficit/hyperactivity disorder, suicide attempts, substance use, and criminality), academic (failing grades and educational attainment), and social (partnering, parenthood, low income, and social welfare benefits) outcomes through 2009. RESULTS: In the population, there was a dose-response relationship between early gestation and the outcome measures. For example, extreme preterm birth (23-27 weeks of gestation) was associated with infant mortality (odds ratio, 288.1; 95% CI, 271.7-305.5), autism (hazard ratio [HR], 3.2; 95% CI, 2.6-4.0), low educational attainment (HR, 1.7; 1.5-2.0), and social welfare benefits (HR, 1.3; 1.2-1.5) compared with offspring born at term. The associations between early gestation and mortality and psychiatric morbidity generally were robust when comparing differentially exposed siblings and controlling for statistical covariates, whereas the associations with academic and some social problems were greatly or completely attenuated in the fixed-effects models. CONCLUSIONS AND RELEVANCE: The mechanisms responsible for the associations between preterm birth and mortality and morbidity are outcome-specific. Associations between preterm birth and mortality and psychiatric morbidity are largely independent of shared familial confounds and measured covariates, consistent with a causal inference. However, some associations, particularly predicting suicide attempt, educational attainment, and social welfare benefits, are the result of confounding factors. The findings emphasize the importance of both reducing preterm birth and providing wraparound services to all siblings in families with an offspring born preterm.